What is the recommended treatment regimen for a patient with Allergic Bronchopulmonary Aspergillosis (ABPA), particularly one with a history of asthma or cystic fibrosis?

Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)

For acute ABPA, initiate either oral prednisolone 0.5 mg/kg/day for 2-4 weeks (tapered over 4 months total) OR oral itraconazole 400 mg/day for 4 months as first-line monotherapy. 1

Treatment Algorithm Based on Disease Classification

Asymptomatic ABPA

• Do not treat with systemic therapy—these patients require monitoring only 1, 2

ABPA-S (Serological ABPA without bronchiectasis)

• Manage as asthma with standard asthma medications (inhaled corticosteroids, bronchodilators) 1, 2
• Reserve systemic ABPA-specific therapy only for:
  • Poor asthma control despite optimal asthma management 1
  • Recurrent exacerbations despite optimal asthma therapy 1
• High-dose inhaled corticosteroids alone are ineffective for ABPA control and should not be used as primary therapy 1, 3

Acute ABPA (Symptomatic ABPA-B or treatment-requiring ABPA-S)

First-line monotherapy options (choose ONE):

Option 1: Oral Prednisolone

• Dose: 0.5 mg/kg/day for 2-4 weeks 1, 4
• Taper and complete over 4 months total duration 1, 4
• Correct vitamin D deficiency before initiating to minimize osteopenia risk 1

Option 2: Oral Itraconazole

• Dose: 400 mg/day in two divided doses for 4 months 4
• Mandatory therapeutic drug monitoring with target trough level ≥0.5 mg/L 4
• Perform monthly liver function tests 4
• Preferred when systemic glucocorticoids are contraindicated 1, 4
• Lower itraconazole levels during first 3 months correlate with higher relapse rates 5

Combination therapy is NOT recommended as first-line 1, 4, though a short course of glucocorticoids (<2 weeks) may be added initially with itraconazole 1, 4

Avoid these agents as first-line:

• Voriconazole, posaconazole, isavuconazole (reserve for itraconazole failure/intolerance) 1
• Biological agents (not first-line for acute ABPA) 1, 4
• Nebulized amphotericin B (poor efficacy in acute ABPA) 1
• Do not combine methylprednisolone with itraconazole (increased Cushing's syndrome risk) 4

Monitoring Treatment Response

Assess response at 8-12 weeks using: 2, 4

• Clinical symptoms (≥50% improvement on assessment scale) 2
• Serum total IgE (should decrease ≥20-35% from baseline) 2, 4
• Chest radiographs (improvement in infiltrates) 2, 4

Ongoing monitoring schedule: 2, 4

• Every 3-6 months for the first year
• Every 6-12 months thereafter
• Include clinical review, serum total IgE, and lung function tests

Management of ABPA Exacerbations

Defining an exacerbation: 1, 2

• Sustained worsening of symptoms ≥2 weeks OR new infiltrates on chest imaging
• PLUS serum total IgE increase ≥50% above the "new baseline" (during prior clinical stability)

Differentiate from other causes of worsening:

• Asthma exacerbation: No IgE elevation, no new infiltrates 1
• Bronchiectasis (infective) exacerbation: No IgE elevation ≥50%, positive sputum cultures 1

Treatment approach: 1, 4

• Treat like newly diagnosed acute ABPA (prednisolone OR itraconazole)
• For recurrent exacerbations (≥2 in past 1-2 years), especially with extensive bronchiectasis: use combination therapy with oral prednisolone PLUS oral itraconazole 1, 2, 4
• Consider combination therapy for patients with blood eosinophils ≥1000 cells/μL and extensive bronchiectasis (≥10 segments) 2, 4
• For exacerbations refractory to oral glucocorticoids, pulse methylprednisolone may be used 1

Treatment-Dependent ABPA (10-25% of patients)

For patients requiring ongoing therapy after initial 4-month treatment: 2

Maintenance options:

• Long-term itraconazole (preferred): Reduces oral glucocorticoid requirements, sputum eosinophils, and exacerbation frequency; requires therapeutic drug monitoring 2, 6
• Nebulized liposomal amphotericin B 25 mg weekly: Significantly prolongs time-to-first exacerbation 2
• Biological agents: Omalizumab has the most evidence, reducing exacerbations, hospitalizations, improving lung function, and decreasing oral steroid requirements 2, 4
  • Other biologics (mepolizumab, benralizumab, dupilumab, tezepelumab) have been used successfully but with less evidence 2

Advanced ABPA with Extensive Bronchiectasis

Adjunctive therapies: 2

• Nebulized hypertonic saline (3-7%, 4-5 mL) to reduce sputum viscosity; pretreat with nebulized salbutamol to prevent bronchospasm
• Nebulized antibiotics or long-term azithromycin for frequent infective exacerbations
  • Critical caveat: Azithromycin with itraconazole can cause QTc prolongation 2
• Long-term oxygen therapy for resting hypoxemia (PaO₂ ≤55 mmHg) 2

Key Clinical Pitfalls

• Do not use high-dose inhaled corticosteroids as monotherapy for acute ABPA—they fail to achieve immunological control 1, 3
• Ensure itraconazole therapeutic drug monitoring—inadequate levels in first 3 months predict relapse 5
• Distinguish ABPA exacerbations from asthma or bronchiectasis exacerbations using IgE levels and imaging 1
• Approximately 50% of patients experience exacerbations after treatment cessation—maintain vigilant monitoring 1, 2
• Patients without Pseudomonas aeruginosa colonization may be more susceptible to ABPA recurrence 5